Atrial fibrillation (AF) is the most common clinical arrhythmia, and accounts for approximately one third of admissions resulting from cardiac rhythm disturbances. An estimated 2.3 million people in North America have AF. During AF, the normal regular sinus rhythm is overwhelmed by disorganized electrical pulses originated from regions in or near an atrium. This can lead to irregular conductions to ventricles, thereby causing inappropriately fast and irregular heart rate. One type of AF is paroxysmal AF which may last from minutes to days before it stops by itself. Another type known as persistent AF may last for over a week and typically requires medication or other treatment to revert to normal sinus rhythm. The third type, permanent AF, is a condition where a normal heart rhythm cannot be restored with treatment. Persistent AF can become more frequent and result in permanent AF.
Congestive heart failure (CHF) is another major cardiovascular epidemic and affects over five million people in the United States alone. CHF is the loss of pumping power of the heart, resulting in the inability to deliver enough blood to meet the demands of peripheral tissues. CHF patients typically have enlarged heart with weakened cardiac muscles, resulting in reduced contractility and poor cardiac output of blood. CHF can affect the left heart, right heart or both sides of the heart, resulting in non-simultaneous contractions of the left ventricle and contractions of the right ventricle. Such non-simultaneous contractions, also known as dyssynchroncy between the left and right ventricles, can further decrease the pumping efficiency of the heart.
There is a close pathophysiological relationship between AF and CHF. A large percentage of CHF patients may experience AF or other types of atrial tachyarrhythmias. AF may facilitate the development or progression of CHF, and CHF can increase the risk for the development of AF. The prevalence of AF in patients with CHF increased in parallel with the severity of CHF.
Atrial tachyarrhythmias, such as AF, can coexist with HF in many CHF patients. AF may facilitate the development or progression of CHF in several ways. For example, during AF, irregularity of the ventricular contractions can result in reduction in left ventricular (LV) filling during short cycles which is not completely compensated for by increased filling during longer cycles. The loss of effective atrial contractile function also contributes to the deterioration of LV filling, particularly in CHF patients with diastolic dysfunction. Presence of untreated or uncontrolled AF may also reduce effectiveness of CHF therapies.
Timely treatment of AF is important in preventing the exacerbating effect of AF on CHF patients. It can also prevent thrombus formation and therefore reduce risk of stroke. Patients with AF frequently experience inappropriately rapid heart rate and irregular ventricular rhythm due to the loss of normal AV synchrony. Based on such characteristic clinical manifestation, AF can be detected from cardiac electrophysiological signals such as electrocardiogram (ECG) or intracardiac electrogram (EGM). Therapy options for treating an AF episode can include pharmacological therapy such as antiarrhythmic drugs, surgical therapy such as catheter ablation, or electrical stimulation therapy such as provided by a bedside or ambulatory electrostimulator such as an implantable medical device (IMD).
Depending on the objectives of AF management, there are two types of AF therapies, namely rate control therapies and rhythm control therapies. The goal of the rate control is to reduce and regularize the ventricular contractions without necessarily correcting the ongoing AF rhythm, so as to achieve improvement in hemodynamic status. The goal of the rhythm control is to correct the AF rhythm, restore and maintain a normal sinus rhythm (NSR). Different types, duration, or other characteristics of AF episodes, and a patient's health status and underlying disease or condition (such as CHF), can all affect efficacy of an AF therapy. For example, pharmacological or electrostimulation rhythm control therapies can be less likely successful in patient experiencing permanent AF. In addition to the therapy type, therapy dosage or parameters that controls the strength or duration of therapy may also affect the AF therapy efficacy. Therefore, it is desirable to have an individualized AF therapy that effectively mitigates the adverse impact of AF episodes on a particular patient.
Efficacy of an AF therapy can be evaluated by examining whether the goal of treatment has been reached, being either a restoration of NSR or a regularization of ventricular contractions with reduced heart rate. However, atrial activity signal such as P wave in an electrocardiogram (ECG) can be a relatively weak signal compared to ventricular activity such as R wave or QRS complex which is produced by ventricular depolarization. Atrial activity signals can also be contaminated by noise, or interfered by various physiologic or environmental conditions. Although a dedicated atrial sensing such as by using an implanted lead placed in or near the atrium can improve atrial signal quality, it is not applicable to patient not indicated for atrial lead implantation. On the other hand, AF detection based on irregular ventricular contractions may suffer from confounding factors such as ventricular ectopic contracts or improper sensing of ventricular contractions, which may also manifest irregularity in R waves or QRS complexes. As such, evaluation of AF therapy efficacy based on atrial rate or regularity of ventricular contraction can be less reliable. Therefore, the present inventors have recognized that there remains a considerable need of systems and methods that can determine an individualized AF therapy and evaluate the efficacy of the individualized AF therapy.
Ambulatory medical devices (AMDs) can be used for monitoring HF patient and detecting HF worsening events. Examples of such ambulatory medical devices can include implantable medical devices (IMDs), subcutaneous medical devices, wearable medical devices or other external medical devices. The ambulatory or implantable medical devices can include physiologic sensors which can be configured to sense electrical activity and mechanical function of the heart, or physical or physiological variables associated with the signs and symptoms of worsening of HF. The medical device can optionally deliver therapy such as electrical stimulation pulses to a target area, such as to restore or improve the cardiac function or neural function.
Some AMDs can include a physiologic sensor that provides diagnostic features. In an example, an AMD can include an impedance sensor to sense the fluid status in the lungs. In another example, an AMD can include sensors for detecting heart sounds. Heart sounds are associated with mechanical vibrations from activity of a patient's heart and the flow of blood through the heart, thus are indicative of a patient's hemodynamic status. Heart sounds recur with each cardiac cycle and are separated and classified according to the activity associated with the vibration. The first heart sound (S1) is associated with the vibrational sound made by the heart during tensing of the mitral valve. The second heart sound (S2) marks the beginning of diastole. The third heart sound (S3) and fourth heart sound (S4) are related to filling pressures of the left ventricle during diastole.
The diagnostic feature provided by the physiologic sensors can indicate a patient's hemodynamic status. For example, heart sounds are useful indicators of proper or improper functioning of a patient's heart, and can be used to assess a patient's hemodynamic status. On the other hand, in patient developing an AF episode, the loss of normal AV synchrony and irregular ventricular rhythm can adversely impact the hemodynamic stability in the patient. The loss of effective atrial contraction may result in a marked decrease in cardiac output, especially for persons with impaired diastolic filling of the ventricles. An ongoing AF can cause more significant hemodynamic deterioration in patients with mitral stenosis, restrictive or hypertrophic cardiomyopathy, pericardial diseases, or ventricular hypertrophy. Therefore, physiologic sensors such as heart sounds sensors can be used to assess adverse hemodynamic impact of the AF event on a patient as well as the improvement of hemodynamic outcome in response to various AF therapies, and determine a desirable AF therapy based on the detected improvement in hemodynamic outcome. Various embodiments described herein can help determining an individualized therapy for treating AF or other atrial tachyarrhythmia episode in a patient or evaluating efficacy of the therapy.
Example 1 can include a system that comprises an AF detection circuit configured to detect an AF episode, one or more programmable therapy circuits configured to generate and deliver to the patient a respective therapy in response to the detection of the AF episode, and a hemodynamic sensor circuit configured to sense a hemodynamic status output indicative of a hemodynamic status of the patient. The system can include a therapy selection circuit coupled to the hemodynamic sensor circuit and the one or more programmable therapy circuit. In response to the detection of the AF episode, the therapy selection circuit can automatically program the one or more programmable therapy circuits to generate and sequentially deliver to the patient a first candidate therapy and a different second candidate therapy. The therapy selection circuit can receive from the hemodynamic sensor circuit a first value of the hemodynamic status output in response to or during the delivery of the first candidate therapy and a second value of the hemodynamic status output in response to or during the delivery of the second candidate therapy, and select a desired therapy based on the first and second values of the hemodynamic status output.
Example 2 can include, or can optionally be combined with the subject matter of Example 1 to optionally include: one or more programmable therapy circuits that can generate and deliver to the patient a respective therapy modality including one or more of a cardiac stimulation therapy, a cardiac ablation therapy, a neurostimulation therapy, a denervation therapy, or a pharmacological therapy; and a therapy selection circuit that can program the programmable therapy circuits to respectively generate and sequentially deliver to the patient the first and second candidate therapies each selected from the one or more of the cardiac stimulation therapy, the cardiac ablation therapy, the neurostimulation therapy, the denervation therapy, or the pharmacological therapy.
Example 3 can include, or can optionally be combined with the subject matter of Examples 2 to optionally include one or more programmable therapy circuits that can generate one or more of ventricular fallback pacing therapy, ventricular rate regularization pacing therapy, atrial anti-tachycardia pacing therapy, atrial cardioversion therapy, or atrial defibrillation therapy.
Example 4 can include, or can optionally be combined with the subject matter of one or any combination of Examples 1 through 3 to optionally include a second candidate therapy which can be of a different therapy modality than the first candidate therapy.
Example 5 can include, or can optionally be combined with the subject matter of one or any combination of Examples 1 through 3 to optionally include a second candidate therapy that differs from the first candidate therapy by at least one therapy parameter associated with therapy generation or configuration, such as a therapy dosage, a therapy duration, or a therapy strength.
Example 6 can include, or can optionally be combined with the subject matter of Examples 5 to optionally include in the first candidate therapy a ventricular fallback pacing therapy where the pacing rate gradually changes to a first lower rate limit (LRL) value within a first specified time period, and the second candidate therapy can be a ventricular fallback pacing therapy where the pacing rate gradually changes to a second LRL value different from the first LRL value within a second specified time period.
Example 7 can include, or can optionally be combined with the subject matter of one or any combination of Examples 1 through 6 to optionally include a therapy selection circuit that can program the one or more programmable therapy circuits to initiate the delivery of the second candidate therapy after a specified recovery time following a cessation of the delivery of the first candidate therapy.
Example 8 can include, or can optionally be combined with the subject matter of one or any combination of Examples 1 through 7 to optionally include in the hemodynamic sensor circuit a heart sound sensor configured to sense a heart sound (HS) signal and a hemodynamic parameter generator circuit configured to detect, using the HS signal, one or more HS components including an S1, an S2, or an S3 heart sound.
Example 9 can include, or can optionally be combined with the subject matter of Examples 8 to optionally include a hemodynamic parameter generator circuit that can determine a HS strength indicative of strength of the HS component including strength of the S1, the S2, or the S3 heart sound; and a therapy selection circuit that can receive, from the hemodynamic parameter generator circuit, a first value of the HS strength in response to or during the delivery of the first candidate therapy and a second value of the HS strength in response to or during the delivery of the second candidate therapy, and to select the first candidate therapy as the desired therapy if the first value of the HS strength is greater than the second value of the HS strength, or select the second candidate therapy as the desired therapy if the second value of the HS strength is greater than the first value of the HS strength.
Example 10 can include, or can optionally be combined with the subject matter of Examples 8 to optionally include a cardiac activity sensor configured to sense a cardiac electrical activity including atrial depolarization or ventricular depolarization. The hemodynamic parameter generator circuit can be used to determine a diastolic timing interval (DTI) using the sensed cardiac electrical activity and the detected HS component; and the therapy selection circuit can receive, from the hemodynamic parameter generator circuit, a first value of DTI in response to or during the delivery of the first candidate therapy and a second value of DTI in response to or during the delivery of the second candidate therapy, and to select the first candidate therapy as the desired therapy if the first value of DTI is greater than the second value of DTI, or select the second candidate therapy as the desired therapy if the second value of DTI is greater than the first value of DTI.
Example 11 can include, or can optionally be combined with the subject matter of Examples 8 to optionally include a cardiac activity sensor configured to sense a cardiac electrical activity including atrial depolarization or ventricular depolarization, wherein the hemodynamic parameter generator circuit can calculate a variability of cardiac timing interval (CTIvar) using the sensed cardiac electrical activity and the detected HS component.
Example 12 can include, or can optionally be combined with the subject matter of Examples 11 to optionally include a hemodynamic parameter generator circuit that can determine the CTIvar including a variability of diastolic timing interval (DTIvar); and a therapy selection circuit that can receive a first value of DTIvar in response to or during the delivery of the first candidate therapy and a second value of DTIvar in response to or during the delivery of the second candidate therapy, and to select the first candidate therapy as the desired therapy if the first value of DTIvar is lower than the second value of DTIvar, or select the second candidate therapy as the desired therapy if the second value of DTIvar is lower than the first value of DTIvar.
Example 13 can include, or can optionally be combined with the subject matter of one or any combination of Examples 1 through 12 to optionally include a therapy selection circuit that can, prior to the delivery of the first and second candidate therapies, receive from the hemodynamic sensor circuit a pre-therapy hemodynamic status output and determine a level of hemodynamic deterioration including a relative change of hemodynamic status in response to the detected AF event, and program the one or more programmable therapy circuits to generate respectively the first and second candidate therapies based on the level of hemodynamic deterioration.
Example 14 can include, or can optionally be combined with the subject matter of one or any combination of Examples 1 through 12 to optionally include a therapy selection circuit that can receive from the hemodynamic sensor circuit a first value of pre-therapy hemodynamic status output before the delivery of the first candidate therapy, and a second value of pre-therapy hemodynamic status output before the delivery of the second candidate therapy; and select a desired therapy based on the first and second values of the hemodynamic status output and the first and second pre-therapy hemodynamic status outputs.
Example 15 can include, or can optionally be combined with the subject matter of Examples 14 to optionally include a therapy selection circuit that can calculate a first relative change from the first pre-therapy hemodynamic status output to the first value of the hemodynamic status output, and a second relative change from the second pre-therapy hemodynamic status output to the second value of the hemodynamic status output; and to select the first candidate therapy as a desired therapy if the first relative change is greater than the second relative change, or select the second candidate therapy as the desired therapy if the second relative change is greater than the first relative change.
Example 16 can include processes of detecting an AF onset event in the patient. When the AF onset event is detected, a first candidate therapy can be automatically programmed and delivered to the patient, and a first value of a hemodynamic status parameter can be sensed from the patient in response to or during the delivery of the first candidate therapy. A second candidate therapy can then be automatically programmed and delivered to the patient, and a second value of a hemodynamic status parameter can be sensed from the patient in response to or during the delivery of the second candidate therapy. The method includes a process of determining a desired therapy based on the first and second values of the hemodynamic status output. In an embodiment, a candidate therapy that leads to more significant improvement in the patient's hemodynamic status can be selected as the desired AF therapy.
Example 17 can include, or can optionally be combined with the subject matter of Examples 16 to optionally include generating first and second candidate therapies each selected from one or more of a cardiac stimulation therapy, a cardiac ablation therapy, a neurostimulation therapy, a denervation therapy, or a pharmacological therapy, wherein the cardiac stimulation therapies can include one or more of ventricular fallback pacing therapy, ventricular rate regularization pacing therapy, atrial anti-tachycardia pacing therapy, atrial cardioversion therapy, or atrial defibrillation therapy.
Example 18 can include, or can optionally be combined with the subject matter of one or any combination of Examples 1 and 17 to optionally include generating a second candidate therapy different from the first candidate therapy by at least one therapy parameter associated with therapy generation or configuration, the at least one therapy parameter including a therapy dosage, a therapy duration, or a therapy strength.
Example 19 can include, or can optionally be combined with the subject matter of one or any combination of Examples 16 through 18 to optionally include sensing a heart sound (HS) strength indicative of strength of an S1, an S2, or an S3 heart sound, and selecting the first candidate therapy as the desired therapy if the first value of the HS strength is greater than the second value of the HS strength, or selecting the second candidate therapy as the desired therapy if the second value of the HS strength is greater than the first value of the HS strength.
Example 20 can include, or can optionally be combined with the subject matter of one or any combination of Examples 16 through 18 to optionally include sensing a cardiac electrical activity including atrial depolarization or ventricular depolarization and sensing HS component including an S1, an S2, or an S3 heart sound, the hemodynamic status parameter including a diastolic timing interval (DTI) determined using the sensed, cardiac electrical activity and the sensed HS component, and selecting the first candidate therapy as the desired therapy if the first value of the DTI is greater than the second value of the DTI, or selecting the second candidate therapy as the desired therapy if the second value of the DTI is greater than the first value of the DTI.
Example 21 can include, or can optionally be combined with the subject matter of one or any combination of Examples 16 through 18 to optionally include sensing a cardiac electrical activity including sensing an atrial depolarization or ventricular depolarization and sensing a HS component including an S1, and S2, or an S3 heart sound, and sensing a hemodynamic status parameter including a variability of cardiac timing interval (CTIvar) determined using the sensed cardiac electrical activity and the sensed HS component.
Example 22 can include, or can optionally be combined with the subject matter of Example 21 to optionally include sensing a first value of variability of diastolic timing interval (DTIvar) in response to or during the delivery of the first candidate therapy, sensing a second value of DTIvar in response to or during the delivery of the second candidate therapy, and electing the first candidate therapy as the desired therapy if the first value of DTIvar is lower than the second value of DTIvar, or select the second candidate therapy as the desired therapy if the second value of DTIvar is lower than the first value of DTIvar.
Example 23 can include, or can optionally be combined with the subject matter of one or any combination of Examples 16 through 18 to optionally include sensing a pre-therapy hemodynamic status output and determining a level of hemodynamic deterioration before the delivery of the first and second candidate therapies, wherein automatically programming the first and second candidate therapies includes programming the first and second candidate therapies based on the level of hemodynamic deterioration.
This Overview is an overview of some of the teachings of the present application and not intended to be an exclusive or exhaustive treatment of the present subject matter. Further details about the present subject matter are found in the detailed description and appended claims. Other aspects of the invention will be apparent to persons skilled in the art upon reading and understanding the following detailed description and viewing the drawings that form a part thereof, each of which are not to be taken in a limiting sense. The scope of the present invention is defined by the appended claims and their legal equivalents.